Shikimate-derived compounds

Anthranilic acid (2-aminobenzoic acid) (see page 126) is another shikimate-derived compound which, as its CoA ester anthraniloyl-CoA, can act as a starter unit for malonate chain extension. Aromatization of the acetate-derived portion then leads to quinoline or acridine alkaloids, according to the number of acetate units incorporated (Figure 3.47). These products are similarly discussed elsewhere, under alkaloids (Chapter 6, page 376). 

In plants, phenylpropanoid and shikimate derived compounds can be combined with one to three units derived from malonyl-CoA to yield... 

Phenylalanine Ammonia-Lyase. The building units of lignin are formed from carbohydrate via the shikimic acid pathway to give aromatic amino acids. Once the aromatic amino acids are formed, a key enzyme for the control of lignin precursor synthesis is phenylalanine ammonia-lyase (PAL) (1). This enzyme catalyzes the production of cinnamic acid from phenylalanine. It is very active in those tissues of the plant that become lignified and it is also a central enzyme for the production of other phenylpropanoid-derived compounds such as flavonoids and coumarins, which can occur in many parts of the plant and in many different organs (35). Radioactive phenylalanine and cinnamic acid are directly incorporated into lignin in vascular tissue (36). 

Alkaloids derived from L-tryptophan hold the indole nucleus in a ring system. The ring system originates in the shikimate secondary compounds building block and the anthranilic acid pathway. It is known that the shikimate block. 

Oxopuupehenol (8), cyanopuupehenol (9), puupehedione (10), and chloropuupe-henone (11) are sesquiterpene-shikimate-derived metabolites isolated from sponges of the orders Verongida31 32 and Dictyoceratida.33 Compounds 8 and 9 showed only weak antima-larial activity, while 10 and 11 were inactive. 

An important shikimate metabolite is podophyllotoxin, an antitumour compound—some podophyllotoxin derivatives are used to combat lung cancer. The compound can be split up notion-ally into two shikimate-derived fragments (shown in red and green). Both are quite different and therejjs obviously a lot of chemistry to do after-the shikimic acid pathway is finished. 

Chemically xanthones (9H-xanthen-9-ones) are heterocychc compounds with the dibenzo-y-pyrone framework (1, Fig. 1). The xanthone nucleus is mun-bered according to a biosynthetic convention with carbons 1-4 being assigned to acetate-derived ring A and carbons 5-8 to the shikimate-derived ring B. The other carbons are indicated as 4a, 4b, 8a, 8b, 9, and 9a for structure elucidation pmposes [4]. 

This second volume on Biosynthesis follows the pattern of Volume 1, with the inclusion of a review of non alkaloidal nitrogenous compounds and the partition of plant phenolic compounds into the two principal divisions, polyketide-derived and shikimate-derived classes. 

Figure 1. Biosynthetic pathway for production of shikimic acid pathway-derived phenolic compounds in higher plants.

The effects of glyphosate on phenolic compound production are two-fold 1) accumulation of phenolic compounds that are derivatives of aromatic amino acids is reduced and 2) pools of phenolic compounds derived from constituents of the shikimate pathway prior to 5-enolpyruvylshikimate-3-phosphate become larger. Assays that do not distinguish between effects on these two groups, such as that for hydroxyphenolics of Singleton and Rossi (18), can lead to equivocal and difficult to interpret results (e.g. 3-5). 

---